Electrical impedance myography

ABSTRACT

Electrical impedance myography (EIM) can be used for the assessment and diagnosis of muscular disorders. EIM includes applying an electrical signal to a region of tissue and measuring a resulting signal. A characteristic of the region of tissue is determined based on the measurement. Performing EIM at different frequencies and/or different angular orientations with respect to a muscle can aid in the assessment and diagnosis. Devices are described that facilitate assessment and diagnosis using EIM.

RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §119(e) to U.S.Provisional Application Ser. No. 60/719,426, entitled “Method andApparatus for Electrical Impedance Myography,” filed on Sep. 21, 2005,which is hereby incorporated by reference in its entirety.

FEDERALLY SPONSORED RESEARCH

This invention was made with Government support under Center forIntegration of Medicine and Innovative Technology (CIMIT) grant numberNS042037. The Government may have certain rights in this invention.

BACKGROUND OF INVENTION

Neuromuscular diseases encompass a large collection of disorders,ranging from relatively mild conditions such as focal compressionneuropathies and nerve root injuries, to severe and life-threateningsyndromes, including amyotrophic lateral sclerosis (ALS) and musculardystrophies. These disorders may lead to muscle atrophy and weakness,caused either by injury to or disease of the neuron (neurogenicdisorders), the neuromuscular junction, or the muscle cell itself(myopathic disorders). Another disorder, disuse atrophy, may occur whena limb is immobilized or a patient is bed-bound for a prolonged periodof time, although not classically considered a neuromuscular disorder,also produces substantial morbidity.

Neuromuscular diseases have been assessed and diagnosed using varioustechniques, including nerve condition studies, needle electromyography,muscle imaging, muscle biopsy and genetic testing. However, the initialassessment of the neuromuscular diseases has advanced relatively littlebeyond conventional needle electromyography and nerve conductiontechniques. Similarly, there have been few good approaches to theassessment of disuse atrophy and dysfunction.

Nerve conduction studies (NCSs) and needle electromyography (EMG) areoften the first tests obtained when evaluating a patient forneuromuscular causes of atrophy. NCSs involve stimulation of a nervewith one set of electrodes and recording the resulting muscle or nervepotential with a second set of electrodes. Although useful forevaluating nerve pathology, NCSs are of limited Use for evaluatingmuscle disease or disuse states. The stimuli can be uncomfortable andonly a relatively limited set of distal muscles in the arms and legs canbe evaluated.

Needle electromyography is geared more specifically to muscleevaluation. Needle electromyography can provide a quick survey ofmuscles to determine whether they are being affected by neurogenicinjury or myopathic injury. However, the test has considerablelimitations. First, needle electromyography is very subjective becausephysicians qualitatively assess the attributes of motor unit actionpotentials (MUAPs) as they rapidly pass across an oscilloscopic display.Second, there are substantial limitations with respect to thesensitivity of needle electromyography. It is a common experienceamongst electromyographers that only with extensive probing are one ortwo questionably abnormal MUAPs identified. Third, the lack ofquantifiable results makes EMG an unsuitable modality for followingdisease progression/remission. Finally, needle EMG remains a somewhatpainful, invasive procedure and can thus only be used in a very limitedfashion in children.

Imaging techniques such as magnetic resonance imaging (MRI) andultrasound have found some use in muscle atrophy assessment. Forexample, MRI can be used to identify muscles with active inflammation toassist with biopsy site choice in patients with myositis. However, MRIhas otherwise remained of limited use since it is difficult to evaluatedifferent areas of the body, is costly, cannot easily assess dynamicmuscle states during muscle contraction, and may not be used in patientswith pacemakers and implanted defibrillators. Ultrasound has foundlimited use in neuromuscular disease and disuse atrophy assessment, andremains very qualitative.

Muscle biopsy is another test for evaluation of muscle disease and canbe helpful in arriving at a specific diagnosis. Muscle biopsy frequentlyyields limited or contradictory information and may be unsuitable formonitoring progression of atrophy because of its inherent invasiveness.Given that many diseases are patchy (i.e., regions of diseased muscletissue is interspersed throughout ostensibly healthy muscle tissue), anegative biopsy does not exclude disease, and repeat biopsies sometimesneed to be performed.

Genetic tests can be very useful for assisting in the evaluation of anumber of mostly rare conditions (such as the muscular dystrophies), butis expensive and not relevant to a variety of the most common, acquiredconditions.

SUMMARY OF INVENTION

Existing techniques for assessing and diagnosing neuromuscular diseasescan be unreliable, subjective and sometimes painful to the patient.Embodiments of the invention relate to methods and devices that canprovide a reliable, quantitative and relatively painless assessment anddiagnoses of neuromuscular diseases, and for assessment of disuseatrophy. Applicant has developed generally non-invasive techniques forcharacterizing muscle tissue, facilitating the assessment, diagnosis,monitoring and/or treatment of characteristics and/or conditions ofmuscle tissue that may be indicative of one or more neuromusculardisorders, including disuse atrophy.

One embodiment according to the present invention includes a method ofdetermining at least one characteristic of a region of tissue, themethod comprising acts of applying a plurality of first electricalsignals to the region of tissue, each of the plurality of firstelectrical signals being applied at a respective one of a plurality oforientations, obtaining a plurality of measurements from the region oftissue, each of the plurality of measurements indicative of a respectiveone of a plurality of second electrical signals, each of the pluralityof second electrical signals resulting from applying a respective one ofthe plurality of first electrical signals, and determining the at leastone characteristic based, at least in part, on the plurality ofmeasurements.

Another embodiment according to the present invention includes a methodof determining at least one characteristic of a region of tissue, themethod comprising acts of applying a plurality of first electricalsignals to the region of tissue, each of the plurality of firstelectrical signals being applied at a respective one of a plurality offrequencies, obtaining a plurality of measurements from the region oftissue, each of the plurality of measurements indicative of a respectiveone of a plurality of second electrical signals, each of the pluralityof second electrical signals resulting from applying a respective one ofthe plurality of first electrical signals, and determining the at leastone characteristic based, at least in part, on the plurality ofmeasurements.

Another embodiment according to the present invention includes a deviceadapted for application to a surface of skin to determine at least onecharacteristic of a region of tissue, the device comprising a firstelectrode adapted to apply a first electrical signal to the region oftissue, a second electrode adapted to detect a second electrical signalat the region of tissue resulting from the application of the firstelectrical signal, a rotatable base on which the first electrode and thesecond electrode are mounted and arranged such that, when the rotatablebase is rotated, the first electrode and the second electrode arerotated with respect to the region of tissue to apply the firstelectrical signal to the region of tissue at a plurality of orientationsand to detect the second electrical signal resulting from theapplication of the first electrical signal at the plurality oforientations, and a measurement component coupled to the secondelectrode to obtain at least one measurement indicative of the secondelectrical signal at each of the plurality of orientations.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings are not intended to be drawn to scale. In thedrawings, each identical or nearly identical component that isillustrated in various figures is represented by a like numeral. Forpurposes of clarity, not every component may be labeled in everydrawing. In the drawings:

FIG. 1 is a diagram illustrating an example of a device that performselectrical impedance myography, according to one embodiment of theinvention;

FIG. 2 is a flow chart illustrating a multi-frequency method ofdetermining a characteristic of a tissue region of an organism,according to one embodiment of the invention;

FIGS. 3A-C show plots of measured electrical parameters versusfrequency, using multi-frequency electrical impedance myography obtainedin accordance with various aspects of the invention;

FIGS. 4A-B are diagrams illustrating an example of a device thatperforms rotational electrical impedance myography, according to oneembodiment of the invention;

FIG. 5 is a diagram illustrating an example of a device that performselectrical impedance myography at a plurality of angles, according toone embodiment of the invention; and

FIG. 6 is a diagram illustrating an example of a hand-held device thatperforms electrical impedance myography, according to one embodiment ofthe invention;

FIG. 7 is a flow chard illustrating a method of performing rotationalelectrical impedance myography, according to one embodiment of theinvention;

FIGS. 8A-C show plots of measured electrical parameters versus angularorientation of the measurement obtained in accordance with variousaspects of the invention; and

FIG. 9 is a three-dimensional plot of measured electrical parametersversus frequency and angular orientation obtained in accordance withvarious aspects of the invention.

DETAILED DESCRIPTION

Embodiments of the invention relate to methods and devices fordetermining a characteristic of a region of tissue by applying anelectrical signal to the region and, in response to applying theelectrical signal, obtaining an electrical measurement of the region oftissue. Such a technique may be referred to as electrical impedancemyography (EIM). Neuromuscular disorders can be assessed and diagnosedbased on the measured electrical signals. In some embodiments, thequantitative nature of the techniques described herein can facilitatethe evaluation of the progress of a neuromuscular disorder. For example,the effectiveness of treatments for neuromuscular disorders, such asnewly-developed drugs, may be evaluated using the techniques describedherein.

To perform an EIM technique, an electrical signal (e.g., electriccurrent) may be applied to the region of tissue using electrodes appliedto the skin. Various characteristics can be determined based on theelectrical parameters that are measured for the region, such as theimpedance, reactance, resistance and/or phase shift. In contrast toexisting techniques for assessing and diagnosing neuromuscular disease,EIM may be more rapid, more quantitative, less invasive and morerepeatable. EIM can be used for the assessment of muscle conditions, andmore specifically, neuromuscular disease. However, it should beappreciated that EIM is not limited to the assessment of neuromusculardisease, as any other suitable tissue characteristic(s) may be measuredusing EIM, such as the amount of muscle atrophy that has occurredthrough disuse of a muscle (or more rarely, hypertrophy), as the aspectsof the invention are not limited in this respect.

Some embodiments of the invention relate to methods and devices forperforming multi-frequency EIM, which involves performing EIM using atleast two different frequencies of electrical signals. Because theelectrical parameters of a muscle can be dependent on the frequency ofan alternating current applied to a muscle, measurements of the muscleimpedance for a plurality of frequencies can be utilized to facilitatediagnosis of muscle condition, and to differentiate between normal andabnormal muscle tissue. Multi-frequency EIM can be performed by varyingthe frequency of the alternating current applied to the muscle or groupof muscles. For example, the frequency that is applied may be in therange between about 2 kHz and about 2 MHz, but the invention is notlimited to this particular frequency range, as any other suitablefrequency range can be used.

The alternating current can be injected via one set of surfaceelectrodes (referred to as current-injecting electrodes), and theresulting voltage patterns can be recorded via a second set of surfaceelectrodes (referred to as voltage-recording electrodes). Based on themeasurement of the injected current's magnitude, an impedance instrumentcan convert the voltage signals into a resistance (R) and reactance (X),for each applied frequency. From these parameters, a phase (θ) may becomputed, for each applied frequency. However, any suitable electricalparameters may be measured and/or calculated for evaluation of muscletissue, as the invention is not limited in this respect.

Some embodiments of the invention relate to a method and apparatus forperforming multidirectional EIM (also referred to as rotational EIM).Because the measured electrical parameters of a muscle can beanisotropic, and therefore dependent on the orientation of themeasurement electrodes relative to the muscle fibers, electricalparameter measurements in a plurality of different directions can beutilized to facilitate diagnosis of muscle condition, and todifferentiate between normal and abnormal muscle tissue.

In some embodiments of the invention, a method and apparatus is providedfor both multi-frequency and multidirectional EIM. Such combinedmeasurements can provide more diagnostic information thanmulti-frequency or multidirectional EIM alone. In some embodiments, amethod and apparatus is provided for performing EIM during contractionof a muscle, referred to as dynamic EIM. The contraction can bevoluntary or electrically induced. In yet other embodiments, acombination of multi-frequency, multidirectional, and/or dynamic EIMmeasurements can also be used to differentiate between different typesof abnormal muscle conditions, including neuromuscular conditions (e.g.,amyotrophic lateral sclerosis (ALS), inflammatory myopathy) andneurogenic conditions. It should be appreciated that any of theaforementioned embodiments can be performed on one or more musclesincluding quadriceps, biceps, tibialis anterior, etc., as the inventionis not limited to any specific muscle or muscle group.

FIG. 1 illustrates an example of an apparatus 100 that may be used toperform multi-frequency EIM, according to one embodiment of theinvention. Apparatus 100 includes electrodes 112-115, and also circuit102 that measures and generates electrical signals using signalmeasurement circuit 104 and signal generation circuit 106. Apparatus 100may include any components in any arrangement capable of deliveringelectrical signals and measuring electrical signals resulting from theelectrical signals delivered, as the aspects of the invention are notlimited in this respect.

In this embodiment, signal generating circuit 106 is coupled to twospaced-apart current-injecting electrodes 112 and 113, which may beapplied to region of tissue 108. Using electrodes 112 and 113, anelectrical signal is applied to region of tissue 108, for example, bypassing an electrical current through the skin and into the region oftissue. The electrical signal that is applied may be any suitablesignal, such as a predetermined voltage potential or a predeterminedcurrent. The electrodes may be isolated from a supply voltage using atransformer or any suitable device, such that a “floating” signal, andapplied to the patient, thus enhancing the safety of the procedure.

In one example, the signal that is applied to current-injectingelectrodes 112 and 113 may be a sinusoidally varying voltage having amagnitude of approximately 1 volt (peak-to-peak) and a frequency between2 kilohertz and 2 megahertz. As a consequence of applying this signal,electric current is injected into region of tissue 108. However, itshould be appreciated that these values of voltage; shape and frequencyare provided merely by way of illustration, as the invention is notlimited in these respects. Furthermore, any suitable circuit and/ortechnique may be used to generate the electrical signal applied to theregion of tissue, as the aspects of the invention are not limited foruse with any particular method of electrical signal generation and/orapplication.

Signal measuring circuit 104 is coupled to two spaced-apartvoltage-measuring electrodes 114 and 115. While the generated signal isapplied to tissue region 108 by signal generation circuit 106, signalmeasurement circuit 104 measures a signal at the tissue region usingvoltage-measuring electrodes 114 and 115. The signal that is measuredmay be a voltage difference between the two electrodes that results fromthe generated signal. Any suitable circuit and/or technique may be usedto measure the signal, as the aspects of the invention are not limitedin this respect.

Circuit 102 may analyze the measured signal and determine acharacteristic of the region of tissue based on the measured signal. Anysuitable property of the signal may be measured, such as the magnitude,phase, impedance, resistance and reactance or any suitable combinationthereof. In some embodiments of the invention, the measured voltagedifference at electrodes 114 and 115 may be divided by the currentapplied through electrodes 112 and 113 to obtain an impedancemeasurement. Circuit 102 may determine an impedance, resistance,reactance, phase and/or any other suitable property of the region. Basedon the measured signal, any of suitable electrical parameters, and/orelectrical properties of the region of tissue, circuit 102 may determinea muscle characteristic. For example, circuit 102 may diagnose and/orassess a neuromuscular disease based on any suitable criteria, asdiscussed in further detail below.

In some circumstances, circuit 102 may display one or more of thedetermined electrical parameters to facilitate diagnosis and/orassessment by a physician or technician. Circuit 102 may include anysuitable components for performing such measurements, calculations,determinations and presentation functions. As one example, circuit 102may include a lock-in amplifier for impedance measurement, a computerfor performing calculations and a display for displaying the results toa human (e.g., a technician or a physician). However, it should beappreciated that any suitable components or combination of componentsmay be used, as the invention is not limited for use with any particularcomponents or configuration of the components.

FIG. 2 is a flowchart of a method 200 for performing multi-frequencyEIM, according to one embodiment of the invention. As described above, afirst signal of a first frequency is applied to a tissue region in step202, and a first signal measurement is made in step 204, such that themeasured signal is a result of applying the first signal of the firstfrequency. Next, a second signal of a second frequency is applied to thetissue region in step 202, and a second signal measurement is made forthe second frequency in step 204. Further signals at differentfrequencies may also be applied, and corresponding measurements may betaken. Any suitable number of frequencies may be used in themulti-frequency EIM procedure, as the invention is not limited as to thenumber of frequencies measured or the exact frequencies at whichmeasurements are taken. Preferably, if multi-frequency EIM is performed,the frequencies used should be of a number and value such that themeasurements are sufficient to provide information useful in assessmentor diagnosis of the tissue region, e.g., the assessment or diagnosis ofa muscle condition.

In step 206, a characteristic of the region of tissue is determinedbased on the measurements. The characteristic that is determined may bea muscle characteristic, and may be determined based on one or moreelectrical properties obtained from the measurements, such as theimpedance, phase, resistance and/or reactance of the muscle. As anotherexample, a frequency-averaged impedance, phase, resistance and orreactance may be determined for at least a portion of the range offrequency measurement. The frequency-averaged parameter may be a usefulparameter for comparing healthy vs. unhealthy tissue, and evaluatingchanges in the tissue over time. For example, a diagnosis of aneuromuscular condition may be made based on a frequency-averagedparameter being above or below a threshold value.

One or more electrical properties obtained from measurements taken fromthe region of tissue as a function of frequency may be used as asignature for the region of tissue. The term signature refers herein toany collection of information obtained from a region of tissue that ischaracteristic of the tissue. The signature of the tissue, onceobtained, may be analyzed to assess, diagnose or otherwise determine acharacteristic and/or condition of the region of tissue.

The signature of the tissue may be computationally processed and/oranalyzed or presented to a physician or technician for analysis. As oneexample, a plot of an electrical parameter vs. frequency (e.g.,resistance, reactance or phase of the tissue vs. frequency) may bedisplayed on a computer monitor, and a physician may make a diagnosisbased on the plot displayed. Multiple plots displaying any of variouselectrical properties of the dime with respect to frequency may bedisplayed, as the aspects of the invention are not limited in thisrespect.

FIGS. 3A-C show plots of resistance, reactance and phase vs. thelogarithm of frequency, respectively, measured for two different ALSpatients (C and J) at two different visits, 3-4 months apart each. Thesolid line shows the measurements taken at the first visits and thedashed lines shows the measurements taken at the follow-up visits.Patient C had relatively mild ALS, while patient J had a more severeform of the disease. As can be readily appreciated from FIGS. 3B-C, thepatient (J) with the more severe muscle disorder had lower phase andreactance values than the patient (C) with the less severe disorder. Atthe follow-up visit, both patients exhibited primarily a decrease inboth phase and reactance measured, which illustrates the progression ofthe disease over time.

Additionally, the patient with less severe ALS had a much morepronounced frequency peak in both reactance and phase than the patientwith the more severe form of ALS. These results are provided toillustrate various criteria that may be used in determiningcharacteristics of a region of tissue using EIM, and which may displayedfor use by a suitable medical practitioner. However, it should beappreciated that any suitable measured and/or calculated criteria may beused for characterization, as the invention is not limited as to theparticular criteria used. In some circumstances, a diagnoses orassessment may be made by circuit 102. For example, circuit 102 may beconfigured to analyze the signature (e.g., one or more electricalproperties as a function of frequency) to determine a characteristic ofthe region of tissue and/or to assess a condition of the region oftissue.

As discussed above, multidirectional (or rotational) EIM may be used forthe assessment and characterization of a region of tissue.Multidirectional BIM can be perforated by measuring the voltagedifference between voltage-measuring electrodes that are arranged with adesired orientation with respect to an axis of the muscle fibers. Boththe current-injecting electrodes and the voltage-recording electrodesmay have the same orientation with respect to the muscle fibers. Theelectrical properties of the region of tissue at various orientationsmay be used to characterize the region of tissue, e.g., to assess acondition of the muscle and/or to perform a diagnosis of the muscle.

FIGS. 4A-B are diagrams illustrating performing EIM at differentorientations with respect to a region of tissue 108. FIGS. 4A-B showelectrodes 112-115, as described above with respect to FIG. 1.Electrodes 112-115 may be mounted on a base 402. FIG. 4A illustratesperforming EIM along a direction A-A aligned with an axis of the regionof tissue 108, e.g., substantially aligned with fibers of the muscle.FIG. 4B illustrates performing HIM along a direction at an angle θ withrespect to the axis. Measurements obtained at the different orientationsmay be used to characterize and/or otherwise assess a condition of theregion of tissue 108. Measurements may be obtained at multipleorientations to obtain information about how properties of the tissuevary with orientation (e.g., to determine a degree of anisotropy of thetissue), as discussed in further detail below.

In one embodiment, electrodes 112-115 are mounted on rotatable base 402,which is made of electrically insulating material. When a measurement isto be taken, electrodes 112-115 are brought into contact with the skinat the region of tissue, and are aligned in a first direction withrespect to an axis of the region. When a second measurement is to betaken, base 402 is rotated by the desired angle θ, and electrodes112-115 are again brought into contact with the skin at the neworientation.

Multiple different measurements may be made at different angles. As oneexample, measurements may be made at six different angles, each 30°apart (0°, 30°, 60°, 90°, 120° and 150°). However, it should beappreciated that any suitable angle increments or number of measurementsat different angles may be used, as the invention is not limited in thisrespect. Preferably, if rotational EIM is performed, the angles usedshould be of a number and increment such that the measurements aresufficient to provide information useful in assessment or diagnosis ofthe tissue region, e.g., the assessment or diagnosis of a musclecondition.

In another embodiment, electrodes 112-115 may be mounted on rotatablebase 402 made of an electrically conductive material. In thisembodiment, the electrically conductive base 402 may be brought intocontact with the skin at the region of measurement, and the electrodesthemselves may not contact the region directly. In one example,electrically conductive base 402 may be anisotropically conductive suchthat it preferentially conducts current in a direction perpendicular tothe base (e.g., into the patient's body). The anisotropy of theconductive base can prevent undesirable cross-talk between theelectrodes, and may allow current to penetrate a greater depth into thetissue region.

FIG. 5 illustrates another embodiment using rotational EIM, in which aplurality of current-injecting electrodes 502 and voltage-measuringelectrodes 504 are mounted on base 402 at different orientations. Sincethe electrodes are mounted at a plurality of different orientations, itmay not be necessary to rotate the electrodes or base 402 to makemeasurements at different angles. When a first measurement is to bemade, an appropriate pair of current-injecting electrodes can beselected and coupled to signal-generating circuit 106 using any suitableswitches. That is, the plurality of electrodes may be configured suchthat the combination of electrodes 502 and 504 at any desiredorientation may be selectively activated.

For example, the current-injecting electrodes that lie along line 506may be selected first. Additionally, the appropriate pair of voltagemeasuring electrodes 504 that lie along line 506 may be selected, andmay be coupled to signal-measuring circuit 104 using any suitableswitches. A first measurement may then be taken along direction 506.When a measurement is to be made along a different direction, theswitches may be reconfigured to couple different electrodes 502 and 504to the appropriate circuits, and measurement may be taken at a differentorientation.

FIG. 6 illustrates an example of a hand-held apparatus 600 that may beused for performing EIM, including rotational and/or multi-frequencyEIM. Providing a hand-held EIM device may facilitate making EIMmeasurements, and thus may reduce the amount of time needed to make themeasurements. Hand-held apparatus 600 may include a handle 602, a userinterface 604, a body 606, base 608 and electrodes 112-115. Theelectrodes may be coupled to circuit 102 in any suitable way, such asthrough a cord attached at the bottom of handle 602, for example. FIG. 6illustrates direction A-A corresponding to direction A-A illustrated inFIG. 4A.

In one embodiment, base 608 may be rotatable, as discussed above, forperforming rotational EIM. In another embodiment, base 608 may not berotatable, but may have a plurality of electrodes 502 and 504 positionedat different orientations, as described in connection with FIG. 5.Apparatus 600 may be configured such that either technique may be used,depending on the type of base/electrode combination that is mounted tothe apparatus. In some circumstances, it may be desirable to providemultiple different base/electrode combinations of different sizes thatmay be easily interchangeable for measuring different types of muscles,or muscles of different sizes. When a different size is needed, the base608 may be detached from apparatus 600 and another base may be attached.

FIG. 7 is a flow chart of a method 700 of performing rotational EIM,according to one embodiment of the invention. In step 702, a firstsignal is applied to a tissue region at a first orientation, and in step704 a second signal, resulting from the first applied signal, ismeasured at the region. Next, a third signal is applied to the tissueregion at a different orientation. For example, a linear electrode arraymay be rotated, and another measurement may be made, as illustrated inFIGS. 4A-B. As another example, if a quasi-circular electrode array isused (FIG. 5), a different set of electrodes may be selected thatcorrespond to a different orientation, and a corresponding measurementmay be made. It is preferred that at least one measurement be made alonga muscle axis, and that at least one measurement be made perpendicularto the muscle axis. Finally, in step 706, a tissue characteristic isdetermined based on the measurements, using any suitable criteria asdiscussed above.

The one or more electrical properties obtained as a function oforientation may be used as a signature of the region of tissue. Asdiscussed above, this signature may be analyzed to determine acharacteristic of the tissue and/or to assess a condition of the muscle.For example, how the one or more electrical properties vary withorientation (e.g., a degree of anisotropy) may be used to assess thehealth of the tissue and/or diagnose a condition such as a specificneuromuscular disorder. The signature may be analyzed quantitatively, orcompared to a reference signature obtained from known healthy ordiseased tissue to assist in the analysis and/or diagnosis of thetissue.

FIGS. 8A-C show plots of resistance, reactance and phase vs. angularorientation, respectively, for both control patients and an ALS patient.As shown in the figures, the measured electrical parameters depend onthe orientation of the measurement with respect to an axis of the musclefibers, with 0° being aligned with the axis. The reactance and phasewere lower for the patient with ALS than for the control patients.Additionally, the control measurements exhibited more significant peaksat 90° in both reactance and phase for the control patients than for thepatient with ALS. These and/or any other suitable criteria may be usedin determining a characteristic of a region of tissue, as these examplesare described merely by way of illustration.

In one embodiment, the frequency dependence and orientation dependenceof one or more electrical properties of a region of tissue are bothexploited to obtain a signature of the region of tissue. For example, ateach of a plurality of orientations, an electrical signal may be appliedat a plurality of frequencies. Measurements of the tissue may be takenfor each frequency at each orientation to determine one or moreelectrical properties of the tissue at the various frequencies andorientations. By obtaining information about both frequency andorientation dependence, a richer set of indicators are available tofacilitate determining a muscle characteristic and/or assessing acondition of the tissue.

FIG. 9 shows a three-dimensional plot 900 illustrating the results ofperforming both multi-frequency and rotational EIM. Overall, the controlpatient exhibited higher phase measurements and more pronounced phasepeaks with respect to both frequency and orientation, as compared to apatient with ALS. Thus, multi-frequency and rotational EIM can beuseful, either alone and in combination, for assessing and detectingneuromuscular disorders. In particular, the quantitative nature of themeasurements may allow for more accurate assessment and diagnoses ofneuromuscular disorders, and also the evaluation of therapies for muscledisorders.

Having thus described several aspects of at least one embodiment of thisinvention, it is to be appreciated various alterations, modifications,and improvements will readily occur to those skilled in the art. Suchalterations, modifications, and improvements are intended to be part ofthis disclosure, and are intended to be within the spirit and scope ofthe invention. Accordingly, the foregoing description and drawings areby way of example only.

Various aspects of the present invention may be used alone, incombination, or in a variety of arrangements not specifically discussedin the embodiments described in the foregoing and is therefore notlimited in its application, to the details and arrangement of componentsset forth in the foregoing description or illustrated in the drawings.The invention is capable of other embodiments and of being practiced orof being carried out in various ways. In particular, various EIMtechniques described herein may be used alone or, in any combination.

Use of ordinal terms such as “first”, “second”, “third”, etc., in theclaims to modify a claim element does not by itself connote anypriority, precedence, or order of one claim element over another or thetemporal order in which acts of a method are performed, but are usedmerely as labels to distinguish one claim element having a certain namefrom another element having a same name (but for use of the ordinalterm) to distinguish the claim elements.

Also, the phraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having,” “containing”, “involving”, andvariations thereof herein, is meant to encompass the items listedthereafter and equivalents thereof as well as additional items.

What is claimed is:
 1. A method of assessing a condition of a region ofmuscle tissue, the method comprising acts of: applying a plurality ofelectrical current signals to the region of muscle tissue, a firstelectrical current signal in the plurality of electrical current signalsbeing applied at a first orientation, the first orientation beingaligned with fibers of a muscle in the region of muscle tissue, and eachother electrical current signal in the plurality of electrical currentsignals being applied to the region of muscle tissue at an angle withrespect to first orientation; obtaining a plurality of electricalvoltage signals, each electrical voltage signal in the plurality ofelectrical voltage signals resulting from applying a respective one ofthe electrical current signals in the plurality of electrical currentsignals; determining at least one electrical property of the region ofmuscle tissue at each orientation of the plurality of orientations todetermine an electrical property profile; and assessing the condition ofthe region of muscle tissue based, at least in part, on the at least oneelectrical property, by comparing the determined electrical propertyprofile with a signature profile of the muscle tissue.
 2. The method ofclaim 1, wherein the act of applying the plurality of electrical currentsignals to the region of muscle tissue includes an act of applying atleast one electrical current signal in a direction perpendicular to thefirst orientation.
 3. The method of claim 2, wherein the act of applyingthe plurality of electrical current signals to the region of muscletissue includes an act of applying at least one electrical currentsignal in a direction parallel to the first orientation and applying atleast one electrical current signal at least every 30 degrees rotationfrom the first orientation over a range of 180 degrees.
 4. The method ofclaim 1, wherein the at least one electrical property is selected fromthe group consisting of resistance, reactance, and phase.
 5. The methodof claim 1, wherein the act of applying the plurality of electricalcurrent signals includes an act of applying a plurality of electricalcurrent signals, each at a respective one of a plurality of frequenciesat each orientation.
 6. The method of claim 5, wherein the act ofobtaining the plurality of electrical voltage signals includes an act ofobtaining at least one electrical voltage signal at each of theplurality of frequencies at each orientation and the act of determiningthe at least one electrical property includes an act of determining atleast one property of the region of muscle tissue at each of theplurality of frequencies at each orientation.
 7. The method of claim 1,wherein the at least one electrical property includes a resistance ofthe region of muscle tissue at the respective orientation.
 8. The methodof claim 1, wherein the at least one electrical property includes areactance of the region of muscle tissue at the respective orientation.9. The method of claim 1, wherein the at least one electrical propertyincludes a phase derived from a resistance and a reactance of the regionof muscle tissue at the respective orientation.
 10. The method of claim1, wherein the act of determining the at least one electrical propertyincludes an act of determining a degree of anisotropy of the firstsignature.
 11. The method of claim 1, wherein the act of determining theat least one electrical property includes an act of comparing the firstsignature with a second signature obtained from a reference region ofmuscle tissue.
 12. The method of claim 11, wherein the second signatureis obtained from healthy muscle tissue.
 13. The method of claim 11,wherein the second signature is obtained from diseased tissue.
 14. Themethod of claim 1, wherein the assessing the condition of the region ofthe muscle tissue comprises assessing the health of the muscle tissue.15. The method of claim 14, wherein assessing the health of the muscletissue comprises diagnosing a specific neuromuscular disorder.
 16. Themethod of claim 15, wherein the specific neuromuscular disorder isselected from the group consisting of focal compression neuropathies,nerve root injuries, ALS, muscular dystrophy, muscle atrophy, musclehypertrophy, disease of the neuron, neurogenic disorders, diseases ofthe neuromuscular junction, diseases of the muscle cell, myopathicdisorders, disuse atrophy, inflammatory myopathy, and neurogenicconditions.
 17. The method of claim 1, further comprising an act ofusing the method to evaluate a treatment for neuromuscular disorders.18. The method of claim 17, wherein the treatment for neuromusculardisorders further comprises use of a drug.
 19. A method of determiningat least one characteristic of a region of tissue, the method comprisingacts of: applying a plurality of first electrical signals to the regionof tissue, a first electrical signal in the plurality of firstelectrical signals being applied at a first orientation and a firstfrequency, and each other first electrical signal in the plurality offirst electrical signals being applied at an angle with respect to thefirst orientation and at one of a plurality of frequencies so as topropagate through at least a portion of the region of tissue in arespectively different direction with respect to the first orientation:obtaining a plurality of measurements from the region of tissue, each ofthe plurality of measurements indicative of a respective one of aplurality of second electrical signals, each of the plurality of secondelectrical signals resulting from applying a respective one of theplurality of first electrical signals, the plurality of measurementsincluding at least one measurement at each of the plurality offrequencies at each of the plurality of orientations; and determiningthe at least one characteristic of the region of tissue based, at leastin part, on the plurality of measurements, wherein the act ofdetermining the at least one characteristic includes an act ofdetermining at least one property of the region of tissue at each of theplurality of frequencies at each of the plurality of orientations, basedon the plurality of measurements; and generating a first signature ofthe region of tissue, the first signature comprising the at least oneproperty as a function of frequency and orientation.
 20. The method ofclaim 19, wherein the plurality of first electrical signals include aplurality of current signals and the plurality of second electricalsignals includes a plurality of voltage signals, each resulting from theapplication of a respective one of the plurality of current signals. 21.The method of claim 19, wherein the at least one property includes aresistance of the region of tissue at the respective frequency and therespective orientation.
 22. The method of claim 19, wherein the at leastone property includes a reactance of the region of tissue at therespective frequency and the respective orientation.
 23. The method ofclaim 19, wherein the at least one property includes a phase derivedfrom a resistance and a reactance of the region of tissue at therespective frequency and the respective orientation.
 24. The method ofclaim 19, wherein the act of determining the at least one characteristicincludes an act of determining a degree of anisotropy of the firstsignature.
 25. The method of claim 19, wherein the act of determiningthe at least one characteristic includes an act of comparing the firstsignature with a second signature obtained from a reference region oftissue.
 26. The method of claim 25, wherein the second signature isobtained from healthy tissue.
 27. The method of claim 25, wherein thesecond signature is obtained from diseased tissue.
 28. The method ofclaim 19, further comprising an act of assessing the health of theregion of tissue based on the at least one characteristic.
 29. Themethod of claim 28, wherein assessing the health of the region of tissuecomprises diagnosing a specific neuromuscular disorder.
 30. The methodof claim 29, wherein the specific neuromuscular disorder is selectedfrom the group consisting of focal compression neuropathies, nerve rootinjuries, ALS, muscular dystrophy, muscle atrophy, muscle hypertrophy,diseases of the neuron, neurogenic disorders, diseases of theneuromuscular junction, diseases of the muscle cell, myopathicdisorders, disuse atrophy, inflammatory myopathy, and neurogenicconditions.
 31. The method of claim 19, further comprising an act ofusing the method to evaluate a treatment for neuromuscular disorders.32. The method of claim 31, wherein the treatment for neuromusculardisorders further comprises use of a drug.